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The human constitutive androstane receptor promotes the differentiation and maturation of hepatic-like cells.

Publication ,  Journal Article
Chen, F; Zamule, SM; Coslo, DM; Chen, T; Omiecinski, CJ
Published in: Dev Biol
December 15, 2013

Expression of the constitutive androstane receptor (CAR, NR1I3) is enriched in the mature mammalian liver and increasingly recognized for its prominent role in regulating a myriad of processes including biotransformation, chemical transport, energy metabolism and lipid homeostasis. Previously, we demonstrated that CAR levels were markedly enhanced during the differentiation of hepatic-like cells derived from hESCs, prompting the hypothesis that CAR contributes a key functional role in directing human hepatogenesis. Here we demonstrate that over-expression of CAR in human embryonic stem cells (ESCs), transduced by a lentiviral vector, accelerates the maturation of hepatic-like cells, with CAR over-expressing cells exhibiting a 2.5-fold increase in albumin secretion by day 20 in culture differentiation, and significantly enhanced levels of mRNA expression of several liver-selective markers, including hepatic transcription factors, plasma proteins, biotransformation enzymes, and metabolic enzymes. CAR over-expressing cells also exhibited enhanced CITCO-inducible CYP3A7 enzymatic activity. Knockdown of CAR via siRNA attenuated the differentiation-dependent expression programs. In contrast, expression levels of the pregnane X receptor (PXR), a nuclear receptor most similar to CAR in primary sequence, were negligible in human fetal liver tissues or in the differentiating hESCs, and stable over-expression of PXR in hepatic-induced hESCs failed to enhance expression of hepatic phenotype markers. Together, these results define a novel role for human CAR in hepatic lineage commitment.

Duke Scholars

Published In

Dev Biol

DOI

EISSN

1095-564X

Publication Date

December 15, 2013

Volume

384

Issue

2

Start / End Page

155 / 165

Location

United States

Related Subject Headings

  • Stem Cells
  • Receptors, Cytoplasmic and Nuclear
  • RNA, Small Interfering
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Liver
  • Humans
  • Embryonic Stem Cells
  • Developmental Biology
  • DNA Primers
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chen, F., Zamule, S. M., Coslo, D. M., Chen, T., & Omiecinski, C. J. (2013). The human constitutive androstane receptor promotes the differentiation and maturation of hepatic-like cells. Dev Biol, 384(2), 155–165. https://doi.org/10.1016/j.ydbio.2013.10.012
Chen, Fengming, Stephanie M. Zamule, Denise M. Coslo, Tao Chen, and Curtis J. Omiecinski. “The human constitutive androstane receptor promotes the differentiation and maturation of hepatic-like cells.Dev Biol 384, no. 2 (December 15, 2013): 155–65. https://doi.org/10.1016/j.ydbio.2013.10.012.
Chen F, Zamule SM, Coslo DM, Chen T, Omiecinski CJ. The human constitutive androstane receptor promotes the differentiation and maturation of hepatic-like cells. Dev Biol. 2013 Dec 15;384(2):155–65.
Chen, Fengming, et al. “The human constitutive androstane receptor promotes the differentiation and maturation of hepatic-like cells.Dev Biol, vol. 384, no. 2, Dec. 2013, pp. 155–65. Pubmed, doi:10.1016/j.ydbio.2013.10.012.
Chen F, Zamule SM, Coslo DM, Chen T, Omiecinski CJ. The human constitutive androstane receptor promotes the differentiation and maturation of hepatic-like cells. Dev Biol. 2013 Dec 15;384(2):155–165.
Journal cover image

Published In

Dev Biol

DOI

EISSN

1095-564X

Publication Date

December 15, 2013

Volume

384

Issue

2

Start / End Page

155 / 165

Location

United States

Related Subject Headings

  • Stem Cells
  • Receptors, Cytoplasmic and Nuclear
  • RNA, Small Interfering
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Liver
  • Humans
  • Embryonic Stem Cells
  • Developmental Biology
  • DNA Primers